Outcome of Smoking Cessation on Airway Remodeling and Pulmonary Inflammation in COPD Patients.

2011·0.05 MB·English

by  Mortaz, Esmaeil

REVIEW ARTICLE
Tanaffos (2011) 10(3), 7-11
©2011 NRITLD, National Research Institute of Tuberculosis and Lung Disease, Iran

Outcome of Smoking Cessation on Airway Remodeling
and Pulmonary Inflammation in COPD Patients

Esmaeil Mortaz 1,2, Mohammad Reza Masjedi 2 and Irfan Rahman 3
1 Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands 2 Chronic
Respiratory Disease Research Center, National Research Institute of Tuberculosis and Lung Disease (NRITLD), Masih Daneshvari
Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran, and 3 Lung Biology and Diseases Program, Department of
Environmental Medicine and Pulmonary Medicine, University of Rochester Medical Center, Rochester, USA.

INTRODUCTION
There are currently more than 1.3 billion tobacco deaths has shifted from 19% female in 1970 to 38.5%
smokers in the world according to the World Health in 1993 (8).
Organization (WHO) (1). It has been demonstrated Cigarette smoking, especially heavy smoking,
that cigarette smoking is the most important risk long duration of smoking, and smoking of high-tar
factor for the development and progression of cigarettes accounts for important factors that
chronic obstructive pulmonary disease (COPD), and contribute to the progression of COPD (9). Cigarette
accounts for about 80% of COPD cases (2, 3). smoke contains more than 4000 deleterious chemical
COPD, a term referring to two respiratory system compounds, of which 200 are very toxic, and 1017
diseases: chronic bronchitis and emphysema, is free radicals/oxidants per puff (10). In general, it has
characterized by an airflow limitation that is not fully been accepted that the treatments available for COPD
reversible. The airflow limitation is usually both reduce the number and severity of exacerbations and
progressive and related to the abnormal inflammatory restablish symptoms. However, available treatment
response of the lungs to inhaled noxious particles or do not aide in tackling the cause and ongoing
gases (4, 5). problems of the disease, and have a limited effect on
It has been reported that 10% to 15% of all slowing down the progression of lung damage and
smokers (6) and up to 26% of heavy smokers inflammation (11).
develop COPD (7). As the prevalence of smoking Smoking cessation is considered as the first
has risen among females and decreased slightly treatment in patients with chronic COPD. Its effect
among males, the sexual distribution of COPD on airway inflammation in COPD is not well

described, although cross-sectional studies suggest
Correspondence to: Irfan Rahman
Address: Department of Environmental Medicine and Pulmonary Medicine, ongoing inflammation in ex-smokers (12). So far,
University of Rochester Medical Center, Rochester, USA smoking cessation is considered the only effective
Email address: [email protected]
8 Smoking Cessation and Airway Remodeling in COPD
treatment for avoiding or reducing the progression of Wright et al. (22) and March et al. (23), for the
COPD (13). There are several smoking cessation first time demonstrated that emphysema was still
medications and devices available commercially. present in guinea pigs and mice after smoke exposure
However, there are contradictory observations followed by a smoking cessation period. Thereafter,
regarding the effect of smoking cessation on airway Vernooy et al (24) found that the long-term LPS
inflammation and remodeling associated with COPD exposure results in irreversible alveolar enlargement
including the use of smoking cessation medications in mice.
and devices. Studies in COPD patients indicated that Recently Braber et al described the alveolar
smoking cessation improves respiratory symptoms, enlargement and right ventricle heart hypertrophy in
reduces loss of pulmonary function and decreases smoke-exposed mice remained unchanged, however
lung inflammation and oxidative stress (14-19), the neutrophilic inflammation of BALF was
whilst some studies indicated that smoking cessation decreased, and levels of IL-12 in BALF remained at
fails to reverse the chronic airway inflammation (19- high levels after smoking cessation. It has been
21). Unfortunately, there is insufficient observation shown that cigarette smoke-enhanced VEGF levels
available regarding the effects of smoking cessation did not significantly change after smoking cessation
on pro-inflammatory mediators levels, which do play (25). In conclusion, animal models of CS-induced
a pivotal role in the pathogenesis of COPD. In the lung emphysema could partially regressed after
following sections, recent studies on the potential smoke-cessation/stopping the CS exposures.
role of cigarette smoke cessation on the progression
and development of COPD is summarized. Clinical observations
Now it is clear that the treatment of COPD should
Evidence of animal modeling of lung emphysema begin at an early stage of the disease and smoking
As indicated earlier, there is contradictory data cessation is an important therapeutic mode in patients
available on the role of quitting cigarette smoking as with COPD. Exposure to cigarette smoke activates
it relates to the development of lungs injury and the inflammatory cascade in the airways, resulting in
inflammation. This is due to the insufficient evidence the production of a number of potent cytokines and
on the effects of smoking cessation and the release of chemokines with accompanying damage to
inflammatory mediators, which do play an important the lung epithelium, increased permeability, and
role in airway inflammation and tissue remodeling recruitment of inflammatory cells into the
seen in COPD. Therefore, an animal model of lungs (26, 27).
cigarette smoke-induced lung emphysema usually is It is known that CS- and other environmental
practical. exposure-induced progressive lung injury and
In this regard, the severity of airway remodeling inflammation play a crucial role in pathogenesis of
and inflammation was assessed by analyzing the COPD. In this scenario, excessive shedding of
alveolar enlargement, heart hypertrophy, and columnar cells may be the initial response, followed
inflammatory cells in the BALF and lung tissue and by the mobilization of neutrophils and then
by determining the profiles of cytokine and
macrophages (26). Both of these inflammatory cells,
chemokine in the BALF of animals.
by releasing the proteases enzymes may be involved
Tanaffos 2011; 10(3): 7-11
Mortaz E, et al. 9
in the breakdown of the supporting connective tissue symptomatic COPD patients, who successfully quit
of the lung. The lung macrophages begin to clean up smoking showed airway inflammation persisted in
the foreign matter, becoming pigmented (28) later, bronchial biopsies, while the number of sputum
mucous gland hypertrophy and excessive production neutrophils, lymphocytes, interleukin (IL)-8, and
of mucus develops, resulting in mucous casts, which eosinophilic-cationic-protein levels significantly
can plug the small airways. This may be followed by increased at 12 months. In the same study of
transformation of the columnar mucosa to a self- asymptomatic smokers who successfully quit,
protective metaplastic and then a potentially inflammation significantly reduced (i.e. the sputum
premalignant dysplastic surface. macrophages, percentage of eosinophils and CXCL-8
It has been shown that quitting smoking induces a levels) or did not change (29). Interestingly, Turato et
generally opposite effects. The numbers of al have described that the inflammatory process
neutrophils and of macrophages dropped present in the airway mucosa of current smokers may
significantly in the first few samples after quitting persist after smoking cessation in subjects
smoking. Columnar cell counts seemed to fall after a who continue to have symptoms of chronic
four- to six-months delay, but statistically when bronchitis (21).
averaged over a twelve month period, there were no
significant changes seen in those who stopped Conclusions, further questions and outlook
smoking compared with those who did not. The As indicated earlier, smoking leads to irreversible
quantity of mucus in the specimens did not fall lung emphysema and heart hypertrophy. The
significantly, although in non-quitters there was a inflammatory process in the airways and lungs of
significant increase over the baseline levels. Whereas COPD patients caused by cigarette smoke exposure
macrophages (non-pigmented and pigmented), were only partially reversed after smoking cessation.
neutrophils, mucus, and columnar cells are present to There still needs to be an increase in the awareness
some degree in all sputa, mucous spirals are not. For of smoking cessation for patients with other disorders
the individual who successfully stopped smoking, such as cardiovascular diseases, however, the
there may be few if any signs of recovery in lung following factors should be of focus for tobacco
function during the critical six months to one year control in the following groups/classes of patients:
when most recidivism occurs (13). younger in age, low socio-economic status, patients
The effects of long-term smoking cessation over a with smoking family members, patients with a higher
five year period, studied by Scanlon et al., described body mass index, and higher total family income.
that participants who stopped smoking experienced In conclusion, it is now clear that smoking
an improvement in FEV1 in the year after quitting cessation should be considered as a first step to halt
(an average of 47 ml or 2%) (15). To gain insight in the decline and progression of lung emphysema,
into the underlying pathophysiological mechanisms inflammation, and oxidative stress. An additional
of cigarette smoke cessation, many laboratories medication and support could be provided to tackle
investigated the airway inflammation in bronchial chronic respiratory symptoms involving
biopsies and sputum samples (29). In one study of inflammation (See table 1).
Tanaffos 2011; 10(3): 7-11
10 Smoking Cessation and Airway Remodeling in COPD

Table 1. Effects of smoking cessation on inflammation cells and lungs function.

Studies Inflammation Disease condition
Skold et al (13) Decreased amount cells in BALF No effects on FEV1
Swan et al. (14) Decreased macrophages, neutrophils Reduction in pulmonary functions
Scanlon et al.(15) Decreased macrophages, neutrophils Improvement of lung function in FEV1
Pelkonen et al. (16) Not reported Reduced decline of FEV1
Godtfredsen et al. (12) Not reported ?
Willemse et al. (20) Increased inflammatory cells in BALF Improved the decline of lung function
Turato et al. (21) Increased number of macrophages in bronchial airways Not reported
Wright et al. (22) lung emphysema is progressive Not reported

Abbreviations:
BALF; Bronchoalveolar lavage fluid; COPD; Chronic Obstructive Pulmonary Disease; CS; Cigarette smoke; ROS; Reactive oxygen species; FEV1; Forced Expiratory Volume

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